The objectives of the proposed work are as follows: In collaboration with Professor Wilbur H. Sawyer, M.D., Ph. D., Department of Pharmacology, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, NY to design and synthesize the following peptides for potential clinical application: 1) Effective in vivo antagonists of oxytocin, 2) Antagonists of the Antidiuretic Response to arginine vasopressin (AVP), 3) Antagonists of the pressor response to AVP, 4) Natriuretic/diuretic peptides, 5) AVP analogs with enhanced pressor/antidiuretic (P/A) selectivity. An additional objective is: 6) To continue to provide other investigators with samples of synthetic peptides for their independent investigations. Results to date for objective 1 and 3 are highly encouraging. We have synthesized a number of analogues of oxytocin which possess potent antagonism to the in vivo oxytocic effects of oxytocin in the rat. These analogues are d(CH2)5Thr4-oxytocin, dP Tyr(Me)2oxytocin and dP Tyr(Me)2 Thr4 oxytocin. Their in vivo PA2 values are in the range of 6.84-6.96. We have also synthesized a number of analogues of AVP which are potent antagonists of the vasopressor effects of AVP. The most potent of these are dP Tyr(Me)AVP, (PA2 7.96), dP Tyr(Me)VDAVP (PA2 7.83) and dP Tyr(Me)2-delta 3-Pro7-AVP (PA2 7.98). These findings have provided very useful clues to the design of even more potent antagonists of oxytocin and AVP. Such antagonists have potential value for a) the prevention of premature labor and b) probing the possible importance of vasopressin in cardiovascular regulation in physiological and pathophysiological states, respectively.